Definition/General

Introduction:
-Phyllodes tumors are rare fibroepithelial tumors of the breast that are classified as benign, borderline, or malignant based on histological features
-Malignant phyllodes tumors account for about 25% of all phyllodes tumors and have the potential for local and distant recurrence.
Origin:
-They arise from the intralobular stroma of the breast
-They are composed of a benign epithelial component and a malignant stromal component.
Classification:
-The classification into benign, borderline, and malignant is based on a combination of features: stromal cellularity, stromal atypia, mitotic activity, stromal overgrowth, and the nature of the tumor borders (pushing vs
-infiltrative).
Epidemiology:
-Phyllodes tumors are most common in women in their 40s
-Malignant phyllodes tumors tend to occur at a slightly older age
-They are rare, accounting for less than 1% of all breast tumors.

Clinical Features

Presentation:
-Typically presents as a large, rapidly growing, palpable breast mass
-The mass is usually firm and mobile
-Skin changes like ulceration can occur with very large tumors.
Symptoms:
-A painless, large breast lump is the most common symptom
-The rapid growth can cause a sensation of pressure or discomfort.
Risk Factors:
-The exact cause is unknown
-They are not strongly associated with the common risk factors for breast carcinoma
-A history of a benign phyllodes tumor or fibroadenoma may be present.
Screening:
-They are usually diagnosed after a palpable mass is investigated
-On mammography, they appear as large, well-circumscribed, lobulated masses
-Ultrasound shows a solid mass, sometimes with cystic spaces.

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Gross Description

Appearance:
-A large, well-circumscribed, lobulated mass
-The cut surface has a characteristic leaf-like (phyllodes) appearance with whorled, fleshy, gray-white tissue and cystic spaces.
Characteristics:
-Malignant tumors are often larger (>5 cm) and may show areas of necrosis and hemorrhage
-The borders can be infiltrative.
Size Location:
-Can occur anywhere in the breast
-Size is highly variable, but malignant tumors are typically large.
Multifocality: Multifocality is rare.

Microscopic Description

Histological Features:
-Biphasic tumor with a benign epithelial component and a malignant stromal component
-The stroma is hypercellular and shows marked atypia, high mitotic activity (>10 per 10 high power fields), and stromal overgrowth (absence of epithelium in at least one low power field).
Cellular Characteristics:
-The stromal cells are spindle-shaped and pleomorphic with hyperchromatic nuclei and frequent, often atypical, mitotic figures
-The epithelial component consists of benign ductal structures.
Architectural Patterns:
-The characteristic leaf-like architecture is formed by the proliferation of the stroma into the cystic spaces lined by epithelium
-Infiltrative borders are a key feature of malignancy.
Grading Criteria:
-The diagnosis of malignant phyllodes tumor is based on the combination of marked stromal hypercellularity, marked stromal atypia, high mitotic rate, stromal overgrowth, and infiltrative margins.

Immunohistochemistry

Positive Markers:
-The stromal cells are positive for vimentin and CD34
-They may show variable positivity for smooth muscle actin and desmin
-The epithelial component is positive for cytokeratins.
Negative Markers:
-The stromal cells are negative for cytokeratins
-Hormone receptors (ER, PR) are usually negative in the stroma but can be positive in the epithelial component
-HER2 is negative.
Diagnostic Utility:
-IHC helps in differentiating from other spindle cell lesions of the breast
-CD34 can be useful
-Ki-67 shows a high proliferation index in the stromal cells.
Molecular Subtypes:
-Not applicable in the same way as for breast carcinomas
-The focus is on the stromal component.

Molecular/Genetic

Genetic Mutations:
-Mutations in MED12 and TERT promoter are common
-Malignant phyllodes tumors show complex karyotypes with numerous chromosomal gains and losses
-TP53 mutations can be seen.
Molecular Markers:
-Overexpression of genes involved in cell cycle progression and proliferation, such as CDK4 and MDM2.
Prognostic Significance:
-Malignant phyllodes tumors have a high risk of local recurrence (around 20-30%) and a risk of distant metastasis (around 20-25%), most commonly to the lungs
-The prognosis is significantly worse than for benign or borderline tumors.
Therapeutic Targets:
-Treatment is primarily surgical, with wide local excision or mastectomy to achieve clear margins
-The role of adjuvant chemotherapy and radiation is not well-established and is considered on a case-by-case basis.

Differential Diagnosis

Similar Entities:
-Fibroadenoma (cellular)
-Metaplastic carcinoma
-Primary breast sarcoma
-Benign or borderline phyllodes tumor.
Distinguishing Features:
-Cellular fibroadenomas lack the marked atypia, high mitotic rate, and stromal overgrowth of malignant phyllodes
-Metaplastic carcinomas have a malignant epithelial component (positive for cytokeratins)
-Primary breast sarcomas lack an epithelial component
-Distinguishing from borderline phyllodes can be difficult and depends on the degree of the histological features.
Diagnostic Challenges:
-The distinction between borderline and malignant phyllodes tumors can be subjective and requires careful evaluation of all histological parameters
-Core biopsy may not be representative of the entire tumor, leading to under-grading.
Rare Variants: Malignant phyllodes tumors can show heterologous stromal differentiation (e.g., liposarcoma, chondrosarcoma, osteosarcoma), which should be noted in the report.

Sample Pathology Report

Template Format

Sample Pathology Report

Complete Report: This is an example of how the final pathology report should be structured for this condition.

Specimen Information

[specimen type], measuring [size] cm in greatest dimension

Diagnosis

[diagnosis name]

Classification

Classification: [classification system] [grade/type]

Histological Features

Shows [architectural pattern] with [nuclear features] and [mitotic activity]

Size and Extent

Size: [X] cm, extent: [local/regional/metastatic]

Margins

Margins are [involved/uninvolved] with closest margin [X] mm

Lymphovascular Invasion

Lymphovascular invasion: [present/absent]

Lymph Node Status

Lymph nodes: [X] positive out of [X] examined

Special Studies

IHC: [marker]: [result]

Molecular: [test]: [result]

[other study]: [result]

Final Diagnosis

Final diagnosis: [complete diagnosis]